Metronidazole for Prevention of Pelvic Cellulitis and Abscess after Laparoscopic Hysterectomy: A Triple-blinded, Randomized, Placebo-controlled Clinical Trial.

STUDY OBJECTIVE: To determine whether a postoperative 5-day treatment schedule with vaginal metronidazole added to conventional antibiotic prophylaxis with 2 g cefazolin modifies the risk of pelvic cellulitis (PC) and pelvic abscess (PA) after total laparoscopic hysterectomy (TLH). DESIGN: A randomized, controlled, triple-blind, multicenter clinical trial. SETTING: Two centers dedicated to minimally invasive gynecologic surgery in Colombia. PATIENTS: A total of 574 patients were taken to TLH because of benign diseases. INTERVENTION: Patients taken to TLH were divided into 2 groups (treatment group, cefazolin 2 g intravenous single dose before surgery + metronidazole vaginal ovules for 5 days postoperatively, control group: cefazolin 2 g intravenous single dose + placebo vaginal ovules for 5 days postoperatively). MEASUREMENTS AND MAIN RESULTS: The absolute frequency (AF) of PC and PA and their relationship with the presence of bacterial vaginosis (BV) were measured. There was no difference in AF of PC (AF, 2/285 [0.7%] vs 5/284 [1.7%] in the treatment and placebo groups, respectively; risk ratio, 1.75; 95% confidence interval, 0.54-5.65; p = .261), nor for PA (AF, 0/285 [0%] vs 2/289 [0.7%]; p = .159, in the treatment and placebo groups, respectively). The incidence of BV was higher in the metronidazole group than the placebo group (42.5% vs 33.4%, p = .026). CONCLUSION: The use of vaginal metronidazole ovules during the first 5 days in postoperative TLH added to conventional cefazolin prophylaxis does not prevent the development of PC or PA, regardless of the patient's diagnosis of BV.

Pelvic surgical site infections in gynecologic surgery.

The development of surgical site infection (SSI) remains the most common complication of gynecologic surgical procedures and results in significant patient morbidity. Gynecologic procedures pose a unique challenge in that potential pathogenic microorganisms from the skin or vagina and endocervix may migrate to operative sites and can result in vaginal cuff cellulitis, pelvic cellulitis, and pelvic abscesses. Multiple host and surgical risk factors have been identified as risks that increase infectious sequelae after pelvic surgery. This paper will review these risk factors as many are modifiable and care should be taken to address such factors in order to decrease the chance of infection. We will also review the definitions, microbiology, pathogenesis, diagnosis, and management of pelvic SSIs after gynecologic surgery.

[Investigation on administration method of carbapenems].

Seventy-two women diagnosed as parametritis were enrolled in this study and examined on the effective administration method of carbapenems, imipenem/cilastatin (IPM/CS), panipenem/betamipron (PAPM/BP) and meropenem (MEPM). The total dosage of each carbapenem was 1.5 g/day, and administration frequency was twice a day (0.75 g x 2) or three times a day (0.5 g x 3). We reviewed the highest body temperature, white blood cell count and CRP value, before treatment and the fourth day after the start of treatment. Three times a day method was statistically superior to twice a day method in the highest body temperature, and CRP value. When we use carbapenem antimicrobial agents, the basis of PK/PD of time above MIC would lead to the increasing clinical effects.

[Obstetrical and gynecological infection].

We discussed the current situation of the intractable bacterial infections in the gyneco-obstetrical field and the countermeasures especially to puerperal fever and pelvic abscess (polymicrobial infection). It is very important to select the proper antibiotics for the treatment, it must be according to the pathobacteriological manifestations of the individual case. We must fix the attention to the infections caused by MRSA.

[Use of ceftriaxone against parametritis after radical surgery for cancer of the uterine cervix].

1. The bacteria isolated from pelvic dead space drainage well reflect the characteristics of prophylactic drugs. As drugs advance from penicillin (PC) to tetracycline (TC) to the first, second and third generation cephems, detection rates for Gram-negative bacilli, mainly Escherichia coli, decrease remarkably, while those for Gram-positive cocci, mainly Enterococcus faecalis, increase. 2. The bacteria isolated from the drainage and those which later caused parametritis and purulent lymphocyst were closely related. It is therefore very important to identify bacteria present in the drainage. 3. Judging from changes occurred in blood levels of ceftriaxone (CTRX) and its effective transfer to the pelvic dead space when CTRX 2 g was administered once daily, this administration regimen is considered to control even parametritis and purulent lymphocyst satisfactorily. 4. CTRX 2 g was administered once daily for 5 consecutive days to each of 4 patients with parametritis, and it was observed that the general efficacy was good in 3 of the 4 cases.

[Basic and clinical studies on cefminox in the field of obstetrics and gynecology].

Basic and clinical studies were carried out on cefminox (CMNX, MT-141), a new cephem antibiotic. Results obtained were as follows. Following each 1 g of intravenous drip infusion and intravenous injection, transfer of CMNX to the internal genital organs was good. Transfer of CMNX into exudate of the pelvic dead space was also good and showed high concentration. CMNX was given to 2 cases. Clinical efficacy was good in 1 case, and could not be evaluated in 1 case. No side effects were observed in both cases. The above results show that CMNX is an effective agent.

[Basic and clinical studies on cefminox in the field of obstetrics and gynecology].

Human pharmacokinetics and clinical studies of cefminox (CMNX, MT-141) were carried out and the following results were obtained. The concentrations of CMNX transferred to the uterus and its appendages after CMNX 1 g intravenous injection were maintained above 12.5 micrograms/g during first 3 hours or more. The concentrations of CMNX transferred to the pelvic dead space exudate were above 12.5 micrograms/ml during 6 hours or more. Those concentrations were sufficiently effective against the major pathogens (Gram-negative and anaerobic bacteria) demonstrated in the field of obstetrics and gynecology. We administered CMNX to 4 cases with postoperative infections at a dose of 2 g per day (twice a day) for a period of 4-6 days. The clinical effect was excellent in 3, good in 1 case. No side effect was observed.

Aztreonam plus clindamycin as therapy for pelvic infections in women.

Aztreonam, a new monobactam antibiotic with specific gram-negative aerobic activity, was used in combination with clindamycin in the treatment of 40 women with pelvic infection, including post-partum endometritis, pelvic inflammatory disease, and post-hysterectomy pelvic cellulitis. Clinical cure was achieved in 87 percent of patients. Failure was related to the limited gram-positive aerobic spectrum of clindamycin. All aerobic gram-negative enteric organisms were sensitive in vitro to less than 0.125 microgram/ml of aztreonam.

[Fundamental and clinical studies on ceftazidime in the field of obstetrics and gynecology].

Fundamental and clinical studies were performed on ceftazidime ( CAZ ), a new cephem antibiotic. Following a single intravenous administration of 1 g dose of CAZ , the transfer of CAZ to the internal genital organs was good. The transfer of CAZ to retroperitoneal fluid was excellent. In a clinical trial, CAZ was given to 6 patients with obstetrical and gynecological infections. The efficacy was evaluated as excellent in 3 cases and good in the other 3 cases. No adverse effects were observed in any of the patients treated with CAZ .

[Clinical use of ceftazidime in the field of obstetrics and gynaecology].

Clinical effect and safety of ceftazidime (CAZ) in the obstetrics and gynaecology were studied in 7 cases of intrauterine infections, 8 cases of parametritis, 1 case of Bartholin's abscess, and 4 cases of intrapelvic infections totalling 20 cases. CAZ was administered at a dose of 2 g per day by intravenous drip infusion, for 4--9 days depending on severity of the disease. The results showed that CAZ was effective in 13 out of 20 cases (overall efficacy rate 65%), and especially in intrauterine infections, it was effective in all the cases. However, effects were not satisfactory in 8 cases of parametritis and 4 cases of intrapelvic infections for various reasons such as influences of underlying diseases including cancer. Neither adverse reactions nor abnormal laboratory findings attributable to CAZ were observed during the treatment.

[Antibiotic therapy in bacterial infections in gynaecology]. / Antibiotikatherapie bei bakteriellen Infektionen in Geburtshilfe und Gynäkologie.

A brief review of the special aspects concerning the use and selection of chemotherapeutic agents and antibiotics in bacterial infections occurring in gynaecology both specifically and generally. In case of severe bacterial infections such as sepsis it is recommended to combine two antibodies (e.g. beta-lactam antibiotics with aminoglycosides or several beta-lactam antibiotics together). Special attention is given to the particularly effective broad-spectrum penicillins and cephalosporins as well as to the aminoglycoside antibiotics etc. Individual well-tried antibiotics are briefly characterised in respect of their anti-bacterial efficacy (sensitivity and resistance), their field of application, and their dosage. In particular, the possibilities of the therapy of infections by anaerobic microorganisms and fungi are pointed out. In addition, a brief description is given of antibacterial chemotherapy of pneumonias of urinary tract infections and specifically gynaecological infections (such as adnexitis, endometritis, parametritis, pelveoperitonitis) under the aspects of rational antibiotic treatment. The article includes by pointing out the possibilities of prophylactic administration of antibiotics especially in surgical procedures in the sense of a perioperative short-term prophylaxis.

Clinical experience with cefotaxime in obstetric and gynecologic infections.

Infections in the upper genital tract continue to be one of the leading causes of serious morbidity for obstetric and gynecologic patients. The polymicrobial, mixed aerobic and anaerobic isolates recovered from women with such infections demand broad-spectrum antimicrobial activity. In the past, combination therapy has been given in order to attain this coverage. In a multicenter open study, cefotaxime was used for treatment of endomyometritis after cesarean section, pelvic cellulitis after hysterectomy, and acute pelvic inflammatory disease. The drug effected a clinical cure in 93% of 104 women. In a randomized comparative study conducted at one center, cefotaxime cured 97% of 36 cases of post-cesarean section endomyometritis; clindamyclin plus gentamicin cured 94% of 18 cases of the same infection. There was no evidence of significant alteration in hematopoietic, hepatic, or renal function with either regimen. Cefotaxime appears to be a safe, extremely effective antimicrobial drug that is ideally suited for single-agent treatment of serious soft-tissue pelvic infections in obstetric or gynecologic patients.

A comparative study of two antibiotic regimens for the treatment of operative site infections.

This prospective study was designed to compare the relative efficacy of two antibiotic regimens for the treatment of operative site infections subsequent to pelvic operations. Patients with endomyoparametritis after delivery or pelvic cellulitis subsequent to hysterectomy were randomized to treatment with the combination of penicillin-gentamicin or the single agent cefoxitin. Seventeen of the 26 patients (65%) with endomyoparametritis who were treated with penicillin-gentamicin were cured by antibiotic therapy alone, in comparison to 15 of 23 (65%) patients treated with cefoxitin. Fifty-eight percent of the patients with pelvic cellulitis who were treated with penicillin-gentamicin responded favorably, in comparison to 50% of the patients treated with cefoxitin. None of these differences was statistically significant. In this study, neither antibiotic regimen provided satisfactory initial treatment for surgically induced soft tissue pelvic infection. Moreover, 11 of the 28 patients with treatment failures (40%) developed serious sequelae of their primary infection.

Moxalactam for obstetric and gynecologic infections. In vitro and dose-finding studies.

Moxalactam (LY 127935), a "third-generation" beta-lactam antimicrobial, has been shown to have promising in vitro activity against a wide spectrum of pathogens similar to those isolated from women with pelvic infections. Pharmacodynamic studies have shown that its serum half life is longer than 2 hours, which permits less frequent dosing. The current investigation was carried out in two parts: In the first phase, the minimal inhibitory concentration of moxalactam against 519 clinical isolates was determined and compared to antimicrobials used in infections caused by these microbes. In vitro activity of moxalactam comparable to that of clindamycin was demonstrated against B. fragilis and other Bacteroides species. There was similar activity to penicillin G and clindamycin against anaerobic gram-positive cocci and activity superior to amikacin was demonstrated against Enterobacteriaceae. The second part of this investigation was a clinical one and 100 women with pelvic infections were given treatment with moxalactam. With an initial dose of 3 gm/day, women with posthysterectomy cellulitis and pelvic inflammatory disease did well. Women with pelvic infections following cesarean section responded less readily to this dose; however, when the initial dose was increased to 6 gm/day, a 91% cure rate was effected. The results of these investigations indicate that moxalactam is useful as a single-agent antimicrobial for treatment of polymicrobial female pelvic infection.

A comparison of two different dosages of pivampicillin and doxycycline in patients with gynaecological infections.

The efficacy of 500 mg pivampicillin twice daily, 350 mg pivampicillin 3-times daily and 100 mg doxycycline daily was compared in 106 patients with salpingitis, parametritis or endometritis. Both the pivampicillin regimens were equally effective. The average duration of therapy needed to produce a satisfactory clinical response was shorter with pivampicillin (14 days) than with doxycycline (21 days). Pivampicillin improved the patients' gynaecological status in 90% of the subjects treated compared to only 70% of patients given doxycycline. Fewer relapses were recorded in women given pivampicillin (4%) than in subjects treated with doxycycline (15%). Gonococci were isolated from 10% of vaginal swabs. The involvement of Chlamydia and Mycoplasma was not studied. However, the high cure rate indicated that, if present, they did not pose a therapeutic problem. Side-effects, mainly dyspepsia, were observed in 2 patients in each group. The twice-daily administration of pivampicillin is recommended, since it is more practical and increases patient compliance.

[Clinical experience of cefoxitin in the field of obstetrics and gynecology (author's transl)].

Cefoxitin was given to the 7 patients of infections in the field of obstetrics and gynecology, and the following results were obtained: 1) The clinical response was excellent in 2 patients, good in 4 and poor in 1 patient with the efficacy rate of 85.7%. Out of the 4 patients resistant to the previous therapy with other antibiotics, 3 patients responded to cefoxitin, and all the 3 patients of anaerobic infections responded satisfactorily to cefoxitin. 2) Microorganisms isolated were 2 strains each of E. coli and Staphylococcus aureus, 3 strains of Peptococcus and 1 strain of Eubacterium lentum. All the 8 strains isolated were sensitive to cefoxitin. As to bacteriological response, all the strains isolated were eradicated except 1 strain of Staphylococcus aureus which recurred on the 9th day after completion of the therapy with the eradication rate of 87.5%. 3) No subjective nor objective side effects were noted. Especially, the elevated GOT and GPT observed on a patient complicated with hepatitis prior to the initiation of cefoxitin treatment were found to be normal upon completion of the treatment.